Eight Hours of Nightly Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea Improves Glucose Metabolism in Patients with Prediabetes. A Randomized Controlled Trial

Abstract

Rationale: Although obstructive sleep apnea (OSA) is associated with impaired glucose tolerance and diabetes, it remains unclear whether OSA treatment with continuous positive airway pressure (CPAP) has metabolic benefits.

Objectives: To determine the effect of 8-hour nightly CPAP treatment on glucose metabolism in individuals with prediabetes and OSA.

Methods: In a randomized controlled parallel group study, 39 participants were randomly assigned to receive either 8-hour nightly CPAP (n = 26) or oral placebo (n = 13). Sleep was polysomnographically recorded in the laboratory on each night. CPAP adherence was ensured by continuous supervision. Participants continued their daily routine activities outside the laboratory. Glucose metabolism was assessed at baseline and after 2 weeks of assigned treatment using both the oral and intravenous glucose tolerance tests. The primary outcome was the overall glucose response as quantified by the area under the curve for glucose during 2-hour oral glucose tolerance testing. Secondary outcomes included fasting and 2-hour glucose and insulin, the area under the curves for insulin and insulin secretion, norepinephrine, insulin sensitivity, acute insulin response to glucose, and 24-hour blood pressure.

Measurements and main results: The overall glucose response was reduced (treatment difference: -1,276.9 [mg/dl] · min [95% confidence interval, -2,392.4 to -161.5]; P = 0.03) and insulin sensitivity was improved (treatment difference: 0.77 [mU/L](-1) · min(-1) [95% confidence interval, 0.03-1.52]; P = 0.04) with CPAP as compared with placebo. Additionally, norepinephrine levels and 24-hour blood pressure were reduced with CPAP as compared with placebo.

Conclusions: In patients with prediabetes, 8-hour nightly CPAP treatment for 2 weeks improves glucose metabolism compared with placebo. Thus, CPAP treatment may be beneficial for metabolic risk reduction. Clinical trial registered with www.clinicaltrials.gov (NCT 01156116).

Trial registration: ClinicalTrials.gov NCT01156116.

Keywords: CPAP; glucose; metabolic; norepinephrine; obstructive sleep apnea.

Figures

Figure 1.

Study protocol. Boxes represent consecutive nights spent in the laboratory (i.e., nights N01–N20) for participants in the oral placebo group (red) and in the continuous positive airway pressure (CPAP) group (blue). At baseline and post-treatment, both groups underwent the same assessments: morning oral glucose tolerance test (OGTT), morning frequently sampled intravenous glucose tolerance test (ivGTT), and 24-hour ambulatory blood pressure (BP) monitoring.

Figure 2.

Participant flow diagram showing the number of participants who were enrolled, underwent laboratory screening testing to assess for eligibility, randomized to each treatment arm, and included in the analysis. CPAP = continuous positive airway pressure.

Figure 3.

Night-by-night polysomnographic data. Average nightly total sleep time (TST; A), apnea–hypopnea index (AHI; B), 3% oxygen desaturation index (ODI; C), and microarousal index (MAI; D) for participants in the oral placebo group (red lines) and in the continuous positive airway pressure group (blue lines) are shown. PRE denotes the three nights recorded during baseline testing period (N01, N02, and N03), and POST denotes the three consecutive nights recorded after treatment during post-treatment testing period (N18, N19, and N20). Participants continued their assigned treatment during the post-treatment testing period. Data are shown in a total of n = 33 participants (excluding three in the continuous positive airway pressure group who withdrew for personal reasons and two who had continuous positive airway pressure intolerance during treatment period). Error bars represent SEM. Dashed lines indicate AHI = 5, ODI = 5, and MAI = 15 events per hour.

Figure 4.

Mean profiles of glucose (left), insulin (middle), and insulin secretion rate (right) during the oral glucose tolerance test for participants in the oral placebo group (red lines) and in the continuous positive airway pressure group (blue lines). Error bars represent SEM.

Figure 5.

Mean profiles of norepinephrine measured during the oral glucose tolerance test for participants in the oral placebo group (red lines) and in the continuous positive airway pressure group (blue lines) are shown. Error bars represent SEM.